Alcohol Use Disorder, Severe
Conditions
Brief summary
Every year, alcohol use disorder (AUD) generates millions of emergency department (ED) visits and hospital admissions, costing the U.S. health sector over $90 billion. These hospital admissions are critical opportunities to start patients on addiction pharmacotherapy, but factors like medication non-adherence and post-discharge relapse contribute to frequent re-admissions. Two single-dose interventions are well suited to facilitate treatment retention and prevent re-admissions due to their prolonged, adherence-independent effects: extended-release (XR) naltrexone injection and intravenous (IV) ketamine infusion. These have not been thoroughly investigated in the hospital setting among high-utilizer, safety-net populations. Therefore, the investigators aim to: 1. Test the feasibility of randomizing hospitalized patients (n=45-60, age 18-65) with multiple AUD-related admissions to treatment with either extended-release (XR) naltrexone, intravenous (IV) ketamine, or no single-dose medication, all with enhanced linkage to care. Feasibility outcomes such as recruitment rate, patient acceptability, post-discharge follow-up rate, and adverse events will help to identify key lessons for a future comparative effectiveness study. 2. Estimate the 30-day re-admission rate for patients randomized to treatment with XR naltrexone, with IV ketamine, or no single-dose medication, all with enhanced linkage to care. The investigators hypothesize that the re-admission rate will be lower for each of the two single-dose medication groups than for the linkage-alone group.
Interventions
XR naltrexone to be given once prior to hospital discharge
DRUGKetamine Hydrochloride
IV ketamine infusion to be given once prior to hospital discharge
BEHAVIORALEnhanced linkage
Includes in-hospital intake at outpatient addiction clinic plus contingency management related to follow-up
Sponsors
Denver Health and Hospital Authority
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Age 18-65 * 1+ alcohol-related\* admission(s) or emergency department visit(s) in past 12 mo. * Has insurance (public or private) * Seen by inpatient addiction consult service
Exclusion criteria
* Known or suspected active COVID-19 infection * Hepatic: AST/ALT \>5x upper-limit of normal, decompensated liver failure * Renal: Glomerular filtration rate \<30ml/min * Cardiovascular: History of acute coronary syndrome, cerebrovascular event, hypertensive crisis, known cardiomyopathy * Known elevated intracranial pressure * Thrombocytopenia (\<50/microliter) * Active moderate/severe withdrawal (based on hospital withdrawal protocol) * Active delirium (alcohol-related or otherwise) * Already enrolled in study * XR naltrexone or IV ketamine in last 30 days * Known intolerance to naltrexone or ketamine * Other active severe substance use disorder (tobacco, cannabis excluded) * Pregnant or breast-feeding, or planning. * Opioids: chronic, recent (\<24h), or anticipated * Unstable psychiatric illness (active psychosis, active suicidality) * Moving from region within 30-days of discharge * Discharge to acute/residential treatment * Involuntary hold
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate (%) of 30-day Hospital Re-admission | Within 30 days of index hospital discharge. The enrollment period is 12 months. | Binary outcome: any all-cause hospitalization ascertained by chart review (our EHR includes records from several local hospitals). Note that it is not dependent on study completion, so it is analyzed by intent to treat. |
| Feasibility - Recruitment Rate (# Per Month) | The enrollment period is 12 months | Number of participants recruited per month during the enrollment period |
| Feasibility - Follow-up Rate (%) | 14 days | Percentage of patients who presented to follow-up appointment within 14 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate (%) of 30-day Emergency Department Visit | Within 30 days of index hospital discharge. The enrollment period is 12 months. | Binary outcome: any all-cause ED visit ascertained by chart review |
Countries
United States
Participant flow
Recruitment details
Hospital.
Participants by arm
| Arm | Count |
|---|---|
| XR Naltrexone Participants will receive a single dose of extended-release, injectable naltrexone prior to hospital discharge, in addition to enhanced linkage to follow-up addiction care.
Naltrexone 380 MG: XR naltrexone to be given once prior to hospital discharge
Enhanced linkage: Includes in-hospital intake at outpatient addiction clinic plus contingency management related to follow-up | 14 |
| IV Ketamine Participants will receive a single dose of intravenous ketamine (0.5mg/kg over 40 minutes) prior to hospital discharge, in addition to enhanced linkage to follow-up addiction care.
Ketamine Hydrochloride: IV ketamine infusion to be given once prior to hospital discharge
Enhanced linkage: Includes in-hospital intake at outpatient addiction clinic plus contingency management related to follow-up | 13 |
| Linkage Participants will receive no single-dose addiction medication prior to hospital discharge, but will receive enhanced linkage to follow-up addiction care.
Enhanced linkage: Includes in-hospital intake at outpatient addiction clinic plus contingency management related to follow-up | 17 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 7 | 5 | 10 |
| Overall Study | Protocol Violation | 2 | 2 | 0 |
Baseline characteristics
| Characteristic | XR Naltrexone | Total | Linkage | IV Ketamine |
|---|---|---|---|---|
| Age, Continuous | 44.9 years STANDARD_DEVIATION 12.5 | 45.1 years STANDARD_DEVIATION 10.9 | 46.2 years STANDARD_DEVIATION 9.5 | 43.9 years STANDARD_DEVIATION 11.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 15 Participants | 5 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 28 Participants | 12 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 4 Participants | 7 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 3 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 8 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 4 Participants | 25 Participants | 12 Participants | 9 Participants |
| Region of Enrollment United States | 14 participants | 44 participants | 17 participants | 13 participants |
| Sex: Female, Male Female | 3 Participants | 9 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 11 Participants | 35 Participants | 15 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 13 | 0 / 17 |
| other Total, other adverse events | 5 / 14 | 6 / 13 | 6 / 17 |
| serious Total, serious adverse events | 0 / 14 | 0 / 13 | 0 / 17 |
Outcome results
Primary
Feasibility - Follow-up Rate (%)
Percentage of patients who presented to follow-up appointment within 14 days
Time frame: 14 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| XR Naltrexone | Feasibility - Follow-up Rate (%) | 7 Participants |
| IV Ketamine | Feasibility - Follow-up Rate (%) | 8 Participants |
| Linkage | Feasibility - Follow-up Rate (%) | 7 Participants |
Primary
Feasibility - Recruitment Rate (# Per Month)
Number of participants recruited per month during the enrollment period
Time frame: The enrollment period is 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| XR Naltrexone | Feasibility - Recruitment Rate (# Per Month) | 3.7 participants per month recruited | Standard Deviation 2.8 |
Primary
Rate (%) of 30-day Hospital Re-admission
Binary outcome: any all-cause hospitalization ascertained by chart review (our EHR includes records from several local hospitals). Note that it is not dependent on study completion, so it is analyzed by intent to treat.
Time frame: Within 30 days of index hospital discharge. The enrollment period is 12 months.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| XR Naltrexone | Rate (%) of 30-day Hospital Re-admission | 3 Participants |
| IV Ketamine | Rate (%) of 30-day Hospital Re-admission | 2 Participants |
| Linkage | Rate (%) of 30-day Hospital Re-admission | 7 Participants |
Secondary
Rate (%) of 30-day Emergency Department Visit
Binary outcome: any all-cause ED visit ascertained by chart review
Time frame: Within 30 days of index hospital discharge. The enrollment period is 12 months.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| XR Naltrexone | Rate (%) of 30-day Emergency Department Visit | 8 Participants |
| IV Ketamine | Rate (%) of 30-day Emergency Department Visit | 7 Participants |
| Linkage | Rate (%) of 30-day Emergency Department Visit | 12 Participants |